Applications of substituent benzyloxy group containing ether compounds for preparing antitumor drugs

ABSTRACT

Disclosed are applications of substituent benzyloxy group containing ether compounds represented by general formula I for preparing antitumor drugs. 
     
       
         
         
             
             
         
       
     
     The definition of the substituent groups in the formula I are provided in the specification. 
     The compounds having general formula I have desirable antitumor activity, particularly, and have excellent activity against leukemia strain HL-60, lung cancer A549, H157, H460, H520, bladder cancer T24, J82, prostate cancer LNCap, PC-3, rectal cancer HCT8, HCT116, RkO and the like.

FIELD OF THE INVENTION

The present invention belongs to the field of medicine, relating to thefield of antitumor drugs. Specifically to applications of substituentbenzyloxy group containing ether compounds for preparing antitumordrugs.

BACKGROUND OF THE INVENTION

The following journals and patents disclosed benzopyrone compoundscontaining methoxyacrylate with fungicidal activity in agrochemicalfield: Pest Management Science, Volume: 67, Issue: 6, Pages: 647-655;Natural Product Communications, Volume: 6, Issue: 12, Pages: 1917-1920;Nongyao, Volume: 50, Issue: 2, Pages: 90-92; Nongyaoxue Xuebao, Volume:12, Issue: 4, Pages: 453-457; Natural Product Communications, Volume: 2,Issue: 8, Pages: 845-848; Chinese Chemical Letters, Volume: 22, Issue:6, Pages: 663-666; WO 2005044813.

Journal of Medicinal Chemistry, Volume: 50, Issue: 12, Pages: 2886-2895reported the following general formula containing benzopyrone group withantiplatelet activity.

Bioorganic & Medicinal Chemistry Letters 23(2013) 3505-3510 disclosed astrobilurin compound containing substituted pyrimidinamines with someantitumor activity, the structure of compound 96 (compound A in thispatent) is as follows:

Patent U.S. Pat. No. 6,084,120 disclosed the compound having followinggeneral formula has some inhibition effect on Plasmodium falciparum NF54strain and plasmodium berghei, however, compound B was reported at thesame time without any biological data. Patent U.S. Pat. No. 7,947,734also disclosed compound B (that is flufenoxystrobin) with goodfungicidal and acaricidal activity in agrochmical field.

In the prior art, the substituent benzyloxy group containing ethercompounds having the structure of general formula I were not reported asantitumor agents.

SUMMARY OF THE INVENTION

The object of the present invention is to provide substituent benzyloxygroup containing ether compounds having general formula I, which can beapplied to prepare antitumor drugs.

Detailed Description of the Invention is as Follows:

The application of substituent benzyloxy group containing ethercompounds for preparing antitumor drugs, the compounds having thestructure of general formula I:

Wherein:

Ar is selected from one of the following groups, Ar1 to Ar16:

Q is selected from one of the following groups, Q1 to Q22:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na,CO₂NH₄, C₁-C₁₂alkyl, C₁-C₁₂haloalkyl, C₃-C₈cycloalkyl, C₁-C₁₂alkoxy,C₁-C₁₂haloalkoxy, C₁-C₁₂alkylthio, C₁-C₁₂haloalkylthio,C₁-C₁₂alkoxyC₁-C₁₂alkyl

haloC₁-C₁₂alkoxyC₁-C₁₂alkyl

C₁-C₁₂alkoxyC₁-C₁₂alkoxy

haloC₁-C₁₂alkoxyC₁-C₁₂alkoxy

C₁-C₁₂alkylthioC₁-C₁₂alkyl

haloC₁-C₁₂alkylthioC₁-C₁₂alkyl

C₁-C₁₂alkylamino

C₁-C₁₂haloalkylamino

C₂-C₁₂dialkylamino

C₂-C₁₂halodialkylamino

piperidinyl

pyrrolidinyl

N-methylpiperidinyl

morpholinyl

C₂-C₁₂alkenyl

C₂-C₁₂haloalkenyl

C₂-C₁₂alkynyl

C₂-C₁₂haloalkynyl

C₂-C₁₂alkenyloxy

C₂-C₁₂haloalkenyloxy

C₂-C₁₂alkynyloxy

C₂-C₁₂haloalkynyloxy

C₁-C₁₂alkylsulfonyl

C₁-C₁₂haloalkylsulfonyl

C₁-C₁₂alkylsulfinyl

C₁-C₁₂haloalkylsulfinyl

C₁-C₁₂alkylcarbonyl

C₁-C₁₂haloalkylcarbonyl

C₁-C₁₂alkylcarbonyloxy

C₁-C₁₂alkylcarbonylamino

C₁-C₁₂alkylsulfonyloxy

C₁-C₁₂alkoxycarbonyl

C₁-C₁₂haloalkoxycarbonyl

C₁-C₁₂alkylaminosulfonyl

C₁-C₁₂alkoxycarbonylamino

C₁-C₁₂alkoxycarbonylC₁-C₁₂alkyl

C₁-C₁₂alkoxycarbonylC₁-C₁₂alkoxy

aminoC₁-C₁₂alkyl

C₁-C₁₂alkylaminoC₁-C₁₂alkyl

C₂-C₁₂dialkylaminoC₁-C₁₂alkyl

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁

SO₂NR₁₀R₁₁

C(═NOR₉)R₈ or R₇; or R₁, R₂ and carbon atom linked to them form five,six or seven-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, phenyloxy,phenyloxy C₁-C₁₂alkyl

phenylcarbonyl

phenyloxycarbonyl

phenylaminocarbonyl

phenylC₁-C₁₂alkyl

phenylC₁-C₁₂alkoxy

phenylC₁-C₁₂alkoxyC₁-C₁₂alkyl

naphthyl

naphthyloxy

naphthyloxy C₁-C₁₂alkyl

naphthylcarbonyl

naphthyl C₁-C₁₂alkyl

naphthyl C₁-C₁₂alkoxy

naphthyl C₁-C₁₂alkoxyC₁-C₁₂alkyl

heteroaryl

heteroaryloxy

heteroarylC₁-C₁₂alkoxyC₁-C₁₂alkyl

heteroaryloxyC₁-C₁₂alkyl

heteroarylcarbonyl

heteroaryloxycarbonyl

heteroarylaminocarbonyl

heteroarylC₁-C₁₂alkyl or heteroarylC₁-C₁₂alkoxy, which is furthermutually independently optionally substituted by 1 to 5 followinggroup(s): halo

NO₂

CN

SH

C₁-C₆alkyl

C₁-C₆ halo alkyl

C₃-C₈cycloalkyl

C₁-C₆alkoxy

C₁-C₆ halo alkoxy

C₁-C₆alkylthio

C₁-C₆ halo alkylthio

C₂-C₆alkenyl

C₂-C₆ halo alkenyl

C₂-C₆alkynyl

halo alkynyl

C₃-C₆alkenyloxy

C₃-C₆ halo alkenyloxy

C₃-C₆alkynyloxy

C₃-C₆ halo alkynyloxy

C₁-C₆alkylsulfinyl

C₁-C₆ halo alkylsulfinyl

C₁-C₆alkylsulfonyl

C₁-C₆ halo alkylsulfonyl

C₁-C₆alkoxyC₁-C₆alkyl

C₁-C₆alkylcarbonyl

C₁-C₆ halo alkylcarbonyl

C₁-C₆alkylcarbonyloxy

C₁-C₆alkylcarbonylamino

C₁-C₆alkylsulfonyloxy

C₁-C₆alkoxycarbonyl

C₁-C₆alkoxyC₁-C₆alkoxy

C₁-C₆alkoxycarbonylC₁-C₆alkyl

C₁-C₆alkoxycarbonylamino

C₁-C₆alkoxycarbonylC₁-C₆alkoxy

CHO

CO₂H

CO₂Na

CO₂NH₄

NR₁₀R₁₁

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H

C₁-C₆alkyl

aryl or aryl C₁-C₆ alkyl;

R₁₀, R₁₁ mutually independently may be the same or different

selected from H

C₁-C₆alkyl

C₁-C₆ halo alkyl

C₁-C₆alkoxy

C₁-C₆ halo alkoxy

C₁-C₆alkylthio

C₁-C₆ halo alkylthio or C₃-C₈cycloalkyl;

And their stereoisomers.

The preferred substituent benzyloxy group containing ether compoundsabove compounds applied as antitumor drugs of general formula I of thisinvention are:

Ar is selected from Ar1

Ar2

Ar3

Ar4 or Ar16;

Q is selected from Q₁

Q₂

Q₃

Q₄

Q₅

Q₆

Q₇

Q₈

Q₉

Q₁₉

Q₂₀

Q₂₁ or Q₂₂:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na,CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio,C₁-C₆alkoxyC₁-C₆alkyl

haloC₁-C₆alkoxyC₁-C₆alkyl

C₁-C₆alkoxyC₁-C₆alkoxy

haloC₁-C₆alkoxyC₁-C₆alkoxy

C₁-C₆alkylthioC₁-C₆alkyl

haloC₁-C₆alkylthioC₁-C₆alkyl

C₁-C₆alkylamino

C₁-C₆haloalkylamino

C₂-C₈dialkylamino

C₂-C₈halodialkylamino

piperidinyl

pyrrolidinyl

N-methylpiperidinyl

morpholinyl

C₂-C₆alkenyl

C₂-C₆haloalkenyl

C₂-C₆alkynyl

C₂-C₆haloalkynyl

C₂-C₆alkenyloxy

C₂-C₆haloalkenyloxy

C₂-C₆alkynyloxy

C₂-C₆haloalkynyloxy

C₁-C₆alkylsulfonyl

C₁-C₆haloalkylsulfonyl

C₁-C₆alkylsulfinyl

C₁-C₆haloalkylsulfinyl

C₁-C₆alkylcarbonyl

C₁-C₆haloalkylcarbonyl

C₁-C₆alkylcarbonyloxyl

C₁-C₆alkylcarbonylamino

C₁-C₆alkylsulfonyloxy

C₁-C₆alkoxycarbonyl

C₁-C₆haloalkoxycarbonyl

C₁-C₆alkylaminosulfonyl

C₁-C₆alkoxycarbonylamino

C₁-C₆alkoxycarbonylC₁-C₆alkyl

C₁-C₆alkoxycarbonylC₁-C₆alkoxy

aminoC₁-C₆alkyl

C₁-C₆alkylaminoC₁-C₆alkyl

C₂-C₈dialkylaminoC₁-C₆alkyl

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁

SO₂NR₁₀R₁₁, C(═NOR₉) R₈ or R₇; or R₁, R₂ and carbon atom linked to themform five or six-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, phenyloxy,phenyloxy C₁-C₆alkyl

phenylcarbonyl

phenyloxycarbonyl

phenylaminocarbonyl

phenylC₁-C₆alkyl

phenylC₁-C₆alkoxy

phenylC₁-C₆alkoxyC₁-C₆alkyl

naphthyl

naphthyloxy

naphthyloxy C₁-C₆alkyl

naphthylcarbonyl

naphthyl C₁-C₆alkyl

naphthyl C₁-C₆alkoxy

naphthylC₁-C₆alkoxyC₁-C₆alkyl

heteroaryl

heteroaryloxy

heteroarylC₁-C₆alkoxyC₁-C₆alkyl

heteroaryloxyC₁-C₆alkyl

heteroarylcarbonyl

heteroaryloxycarbonyl

heteroarylaminocarbonyl

heteroarylC₁-C₆alkyl or heteroarylC₁-C₆alkoxy, which is further mutuallyindependently optionally substituted by 1 to 5 following group(s): halo

NO₂

SH

C₁-C₄alkyl

C₁-C₄ haloalkyl

C₃-C₆cycloalkyl

C₁-C₄alkoxy

C₁-C₄ halo alkoxy

C₁-C₄alkylthio

C₁-C₄ halo alkylthio

C₂-C₄alkenyl

C₂-C₄ halo alkenyl

C₂-C₄alkynyl

C₂-C₄ halo alkynyl

C₃-C₄alkenyloxy

C₃-C₄halo alkenyloxy

C₃-C₄alkynyloxy

C₃-C₄ halo alkynyloxy

C₁-C₄alkylsulfinyl

C₁-C₄ halo alkylsulfinyl

C₁-C₄alkylsulfonyl

C₁-C₄ halo alkylsulfonyl

C₁-C₄alkoxyC₁-C₄alkyl

C₁-C₄alkylcarbonyl

C₁-C₄ halo alkylcarbonyl

C₁-C₄alkylcarbonyloxy

C₁-C₄alkylcarbonylamino

C₁-C₄alkylsulfonyloxy

C₁-C₄alkoxycarbonyl

C₁-C₄alkoxyC₁-C₄alkoxy

C₁-C₄alkoxycarbonylC₁-C₄alkyl

C₁-C₄alkoxycarbonylamino

C₁-C₄alkoxycarbonylC₁-C₄alkoxy

CHO

CO₂H

CO₂Na

CO₂NH₄

NR₁₀R₁₁

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H

C₁-C₄alkyl

aryl or aryl C₁-C₄alkyl;

R₁₀, R₁₁ mutually independently may be the same or different

selected from C₁-C₄alkyl

C₁-C₄ halo alkyl

C₁-C₄alkoxy

C₁-C₄ halo alkoxy

C₁-C₄alkylthio

C₁-C₄ halo alkylthio or C₃-C₆cycloalkyl.

The preferred substituent benzyloxy group containing ether compoundsabove compounds applied as antitumor drugs of general formula I of thisinvention are:

Ar is selected from Ar1, Ar2, Ar3, Ar4 or Ar16;

Q is selected from Q₁

Q₂

Q₃

Q₄

Q₅

Q₆

Q₇

Q₈

Q₉

Q₁₉

Q₂₀

Q₂₁

or Q₂₂:

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na,CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy,C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio,C₁-C₄alkoxyC₁-C₄alkyl

haloC₁-C₄alkoxyC₁-C₄alkyl

C₁-C₄alkoxyC₁-C₄alkoxy

haloC₁-C₄alkoxyC₁-C₄alkoxy

C₁-C₄alkylthioC₁-C₄alkyl

haloC₁-C₄alkylthioC₁-C₄alkyl

C₁-C₄alkylamino

C₁-C₄haloalkylamino

C₂-C₆dialkylamino

C₂-C₆halodialkylamino

piperidinyl

pyrrolidinyl

N-methylpiperidinyl

morpholinyl

C₂-C₄alkenyl

C₂-C₄haloalkenyl

C₂-C₄alkynyl

C₂-C₄haloalkynyl

C₂-C₄alkenyloxy

C₂-C₄haloalkenyloxy

C₂-C₄alkynyloxy

C₂-C₄haloalkynyloxy

C₁-C₄alkylsulfonyl

C₁-C₄haloalkylsulfonyl

C₁-C₄alkylsulfinyl

C₁-C₄haloalkylsulfinyl

C₁-C₄alkylcarbonyl

C₁-C₄haloalkylcarbonyl

C₁-C₄alkylcarbonyloxy

C₁-C₄alkylcarbonylamino

C₁-C₄alkylsulfonyloxy

C₁-C₄alkoxycarbonyl

C₁-C₄haloalkoxycarbonyl

C₁-C₄alkylaminosulfonyl

C₁-C₄alkoxycarbonylamino

C₁-C₄alkoxycarbonylC₁-C₄alkyl

C₁-C₄alkoxycarbonylC₁-C₄alkoxy

aminoC₁-C₄alkyl

C₁-C₄alkylaminoC₁-C₄alkyl

C₂-C₆dialkylaminoC₁-C₄alkyl

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁

SO₂NR₁₀R₁₁

C(═NOR₉)R₈ or R₇; or R₁, R₂ and carbon atom linked to them formsaturated five or six-membered ring;

R₇ is selected from unsubstituted or substituted phenyl

phenyloxy

phenyloxy C₁-C₄alkyl

phenylcarbonyl

phenyloxycarbonyl

phenylaminocarbonyl

phenylC₁-C₄alkyl

phenylC₁-C₄alkoxy

phenylC₁-C₄alkoxyC₁-C₄alkyl

naphthyl

naphthyloxy

naphthyloxy C₁-C₄alkyl

naphthylcarbonyl

naphthyl C₁-C₄alkyl

naphthyl C₁-C₄alkoxy

naphthylC₁-C₄alkoxyC₁-C₄alkyl

heteroaryl

heteroaryloxy

heteroarylC₁-C₄alkoxyC₁-C₄alkyl

heteroaryloxyC₁-C₄alkyl

heteroarylcarbonyl

heteroaryloxycarbonyl

heteroarylaminocarbonyl

heteroarylC₁-C₄alkyl or heteroarylC₁-C₄alkoxy

which is further mutually independently optionally substituted by 1 to 5following group(s): halo

NO₂

CN

SH

C₁-C₄alkyl

C₁-C₄ haloalkyl

C₃-C₆cycloalkyl

C₁-C₄alkoxy

C₁-C₄haloalkoxy

C₁-C₄alkylthio

C₁-C₄ halo alkylthio

C₂-C₄alkenyl

C₂-C₄ halo alkenyl

C₂-C₄alkynyl

C₂-C₄ halo alkynyl

C₃-C₄alkenyloxy

C₃-C₄halo alkenyloxy

C₃-C₄alkynyloxy

C₃-C₄ haloalkynyloxy

C₁-C₄alkylsulfinyl

C₁-C₄ halo alkylsulfinyl

C₁-C₄alkylsulfonyl

C₁-C₄ halo alkylsulfonyl

C₁-C₄alkoxyC₁-C₄alkyl

C₁-C₄alkylcarbonyl

C₁-C₄ halo alkylcarbonyl

C₁-C₄alkylcarbonyloxy

C₁-C₄alkylcarbonylamino

C₁-C₄alkylsulfonyloxy

C₁-C₄alkoxycarbonyl

C₁-C₄alkoxyC₁-C₄alkoxy

C₁-C₄alkoxycarbonylC₁-C₄alkyl

C₁-C₄alkoxycarbonylamino

C₁-C₄alkoxycarbonylC₁-C₄alkoxy

CHO

CO₂H

CO₂Na

CO₂NH₄

NR₁₀R₁₁

C(═O)NR₁₀R₁₁

OC(═O)NR₁₀R₁₁

C(═S)NR₁₀R₁₁ or SO₂NR₁₀R₁₁:

R₈, R₉ is mutually independently selected from H

C₁-C₄alkyl

aryl or aryl C₁-C₄alkyl;

R₁₀, R₁₁ mutually independently may be the same or different

selected from H

C₁-C₄alkyl

C₁-C₄ haloalkyl

C₁-C₄alkoxyl

C₁-C₄ haloalkoxy

C₁-C₄alkylthio

C₁-C₄ haloalkylthio or C₃-C₆cycloalkyl.

Furthermore, the preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

Ar is selected from Ar1

Ar2

Ar3 or Ar16;

Q is selected from Q₁

Q₂

Q₃

Q₄

Q₅

Q₆

Q₇ or Q₈;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl,C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio,C₁-C₄alkoxyC₁-C₄alkyl

C₁-C₄alkylamino

C₂-C₆dialkylamino

C₁-C₄alkylsulfonyl or R₇; or R₁, R₂ and carbon atom linked to them formsaturated five or six-membered ring;

-   -   R₇ is selected from unsubstituted or substituted phenyl, benzyl,        phenylethyl or heteroaryl, which is further mutually        independently optionally substituted by 1 to 5 following        group(s): halo        NO₂        CN        C₁-C₄alkyl        C₁-C₄ haloalkyl        C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

Ar is selected from Ar1, Ar2, Ar3 or Ar16;

Q is Q₁;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl or R₇;or R₁, R₂ and carbon atom linked to them form saturated five orsix-membered ring;

-   -   R₇ is selected from unsubstituted or substituted phenyl, benzyl        or heteroaryl, which is further mutually independently        optionally substituted by 1 to 5 following group(s): halo        NO₂        CN        C₁-C₄alkyl        C₁-C₄ haloalkyl        C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

Ar is selected from Ar3 or Ar16;

Q is Q₁;

R₁, R₂, R₃, R₄, R₅, R₆ mutually independently may be the same ordifferent, selected from H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl or R₇;or R₁, R₂ and carbon atom linked to them form saturated five orsix-membered ring;

R₇ is selected from unsubstituted or substituted phenyl, benzyl orheteroaryl, which is further mutually independently optionallysubstituted by 1 to 5 following group(s): halo

NO₂

CN

C₁-C₄alkyl

C₁-C₄ haloalkyl

C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

-   -   Ar is selected from Ar3 or Ar16;    -   Q is Q₁;    -   R₁ is selected from H, halo or C₁-C₆alkyl;    -   R₂ is selected from C₁-C₄alkyl, C₁-C₄haloalkyl or R₇;    -   Or R₁, R₂ and carbon atom linked to them form saturated five or        six-membered ring;    -   R₃, R₄ are H;    -   R₆ is selected from H or C₁-C₄alkyl;    -   R₇ is selected from unsubstituted or substituted phenyl, which        is further mutually independently optionally substituted by 1 to        3 following group(s); halo, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,        C₁-C₄alkoxy or C₁-C₄ haloalkoxy.

Furthermore, the preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

-   -   Ar is selected from Ar3 or Ar16;    -   Q is Q₁;    -   R₁ is selected from H, halo or C₁-C₆alkyl;    -   R₂ is selected from C₁-C₄alkyl or R₇;    -   Or R₁, R₂ and carbon atom linked to them form saturated five or        six-membered ring;    -   R₃, R₄ are H;    -   R₆ is selected from H or C₁-C₄alkyl;    -   R₇ is selected from unsubstituted or substituted phenyl, which        is further mutually independently optionally substituted by 1 to        3 following group(s): halo, C₁-C₄alkyl, C₁-C₄alkoxy or C₁-C₄        haloalkoxy.

The more preferred substituent benzyloxy group containing ethercompounds above compounds applied as antitumor drugs of general formulaI of this invention are:

-   -   Ar is selected from Ar3 or Ar16;    -   Q is Q₁;    -   R₁ is selected from H, F or C₁-C₄alkyl;    -   R₂ is selected from C₁-C₄alkyl or phenyl;    -   Or R₁, R₂ and carbon atom linked to them form saturated        six-membered ring;    -   R₃, R₄ are H;    -   R₆ is selected from H or CH₃.

The most preferred substituent benzyloxy group containing ethercompounds applied as antitumor drugs of general formula I of thisinvention are:

-   -   Ar is selected from Ar3 or Ar16;    -   Q is Q₁;    -   R₁ is selected from H or C₁-C₄alkyl;    -   R₂ is selected from CH₃ or phenyl;    -   Or R₁, R₂ and carbon atom linked to them form saturated        six-membered ring;    -   R₃, R₄, R₆ are H.

The terms used above to definite the compounds of general formula Irepresent substitutes as follow:

The “halogen” or “halo” is fluorine, chlorine, bromine or iodine.

The “alkyl” stands for straight or branched chain alkyl, such as methyl,ethyl, propyl, isopropyl or tert-butyl. The “haloalkyl” stands forstraight or branched chain alkyl, in which hydrogen atoms can be all orpartly substituted with halogen, such as chloromethyl, dichloromethyl,trichlororaethyl, fluoromethyl, difluoromethyl, trifluoromethyl, etc.

The “alkoxy” refers to straight or branched chain alkyl, which is linkedto the structure by oxygen atom. The “haloalkoxy” refers to straight orbranched chain alkoxy, in which hydrogen atoms may be all or partlysubstituted with halogen, such as chloromethoxy, dichloromethoxy,trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy,chlorofluoromethoxy, trifluoroethoxy, etc.

The “alkylthio” refers to straight or branched chain alkyl, which islinked to the structure by sulfur atom. The “haloalkylthio” refers tostraight or branched chain alkylthio, in which hydrogen atoms may be allor partly substituted with halogen, such as chloromethylthio,dichloromethylthio, trichloromethylthio, fluoromethylthio,difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, etc.

The “alkoxyalkyl” means alkoxy is linked to the structure by alkyl. Suchas —CH₂OCH₂, —CH₂OCH₂CH₃.

The “haloalkoxyalkyl” refers to alkoxyalkyl, in which hydrogen atoms maybe all or partly substituted with halogen, such as —CH₂OCH₂CH₂Cl.

The “alkoxyalkoxy” means OCH₂OCH₂CH₃ etc. The “haloalkoxyalkoxy” means—OCH₂OCH₂CH₂Cl etc.

The “alkylthioalkyl” means alkylthio is linked to the structure byalkyl. Such as —CH₂SCH₂.

The “haloalkylthioalkyl” means haloalkylthio is linked to the structureby alkyl.

The “alkylamino” refers to straight or branched chain alkyl, which islinked to the structure by nitrogen atom.

The “haloalkylamino” refers to straight or branched chain alkylamino, inwhich hydrogen atoms may be all or partly substituted with halogen.

The alkenyl refers to straight or branched chain alkenyl, such asethenyl, 1-propenyl, 2-propenyl and different isomer of butenyl,pentenyl and hexenyl. Alkenyl also includes polyene, such aspropa-1,2-dienyl and hexa-2,4-dienyl. The haloalkenyl stands forstraight or branched chain alkenyl, in which hydrogen atoms can be allor partly substituted with halogen. The alkynyl refers to straight orbranched chain alkynyl, such as ethynyl, 1-propynyl and different isomerof butynyl, pentynyl and hexynyl. Alkynyl also includes groups includingmore than one triple bonds, such as hexa-2,5-diynyl. The “haloalkynyl”stands for straight or branched chain alkynyl, in which hydrogen atomscan be all or partly substituted with halogen.

The alkenoxyl refers to straight or branched chain alkynes is linked tothe structure by oxygen, such as propenyloxy. The haloalkenoxyl standsfor a straight-chain or branched alkenoxyl, in which hydrogen atoms maybe all or partly substituted with halogen. The alkynoxyl refers tostraight or branched chain alkynes is linked to the structure by oxygen,such as propynyloxy. The haloalkynoxyl stands for a straight-chain orbranched alkynoxyl, in which hydrogen atoms may be all or partlysubstituted with halogen.

The “alkylsulfonyl” means a straight-chain or branched alkyl is linkedto the structure by (—SO₂—), such as methylsulfonyl. The“haloalkylsulfonyl” stands for a straight-chain or branchedalkylsulfonyl, in which hydrogen atoms may be all or partly substitutedwith halogen.

The “alkylsulfinyl” means a straight-chain or branched alkyl is linkedto the structure by (—SO—), such as methylsulfinyl.

The “haloalkylsulfinyl” stands for a straight-chain or branchedalkylsulfinyl, in which hydrogen atoms may be all or partly substitutedwith halogen.

The “alkylcarbonyl” means alkyl is linked to the structure by carbonyl.such as CH₃CO—, CH₃CH₂CO—.

The “haloalkylcarbonyl” stands for a straight-chain or branchedalkylcarbonyl, in which hydrogen atoms may be all or partly substitutedwith halogen, such as CF₃CO—.

The “alkylcarbonyloxy” means CH₃COO—, CH₃CH₂NHCOO— etc. The“alkylcarbonylamino” means CH₃CONH—, CH₃CH₂NHCONH— etc.

The “alkylsulfonyloxy” means alkyl-S(O)₂—O—. The “alkoxycarbonyl” meansalkyl-O—CO—.

The “haloalkoxycarbonyl” stands for alkoxycarbonyl, in which hydrogenatoms can be all or partly substituted with halogen, such as —COOCH₂CF₃,—COOCH₂CH₂Cl.

The “alkylaminosulfonyl” means —S(O)₂NHCH₃, —S(O)₂NHCH₂CH₃ etc. The“alkoxycarbonylamino” means —NHCOOCH₃, —NHCOOCH₂CH₃ etc. The“alkoxycarbonylalkyl” means —CH₂COOCH₃, —CH₂COOCH₂CH₃ etc. The“alkoxycarbonylalkoxy” means —OCH₂COOCH₃, —OCH₂COOCH₂CH₃ etc. The“aminoalkyl” such as —CH₂NH₂, —CH₂CH₂NH₂. The “alkylaminoalkyl” such asCH₂NHCH₃, —CH₂NHCH₂CH₃. The “dialkylaminoalkyl” such as —CH₂NH(CH₃)₂etc.

The “aryl” in terms of (hetero)aryl, (hetero)aryloxy,(hetero)arylalkoxyalkyl, (hetero)aryloxyalkyl, (hetero)arylcarbonyl,(hetero)aryloxycarbonyl, (hetero)arylaminocarbonyl, (hetero)arylalkyl or(hetero)arylalkoxy include phenyl or naphthyl etc.

The heteroaryl stands for five member ring or six member ring containingone or more N, O, S hetero atoms. Such as pyridinyl, pyrimidinyl,pyrazinyl, pyridazinyl, triazinyl, furyl, thiazolyl, quinolinyl,isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl,pyrazolyl, pyranyl, triazolyl, tetrazolyl, benzothiazolyl, benzofuranyl,etc. The (hetero)aryloxy such as phenyloxy, pyridinyloxy,pyrimidinyloxy, quinolinyloxy, eye.

The (hetero)arylalkoxyalkyl means —CH₂OCH₂Ph,6-chloropyridin-3-ylmethoxyl, etc. The (hetero)aryloxyalkyl means,—CH₂OPh, 4,6-(OCH₃)₂-2-yloxyethyl, etc. The (hetero)arylcarbonyl meansPhCHO, 4-ClPhCHO, etc. The (hetero)aryloxycarbonyl means PhOCO,4-ClPhOCO, 4-NO₂PhOCO, Naph OCO, etc. The (hetero)arylaminocarbonyl,(hetero)arylalkyl or (hetero)arylalkoxy includes phenyl or naphthyl etc.

The compounds of the present invention can form stereoisom (Z- andE-isomer respectively) due to the existing of C═C and C═N bonds. Theinvention includes Z-isomer and E-isomer and their mixture at any ratio.

The drugs were made from the active ingredients of general formula Isubstituent benzyloxy group containing ether compounds, which can doseby oral medication or parenteral route, also by implantable medicationpump and other methods.

The substituent benzyloxy group containing ether compounds having thegeneral formula I in present invention can be used to prepare the drugsfor curing or alleviating the cancer. The formulations include tablets,pills, capsule, granule, syrup, injection or freeze-dried powderinjection.

Furthermore, the substituent benzyloxy group containing ether compoundshaving the general formula I in present invention can be used to cure oralleviate the cancer causing by cancer cells of human tissue or organ.The cancers include but not limited to colon cancer, liver cancer, lymphcancer, lung cancer, esophageal cancer, breast cancer, central nervoussystem cancer, melanoma, ovarian cancer, cervical cancer, renal cancer,leukemia, prostatic cancer, pancreatic cancer, bladder cancer, rectalcancer or stomach cancer.

Part of the substitutes of R₁, R₂, R₃, R₄, R₅ and R₆ in formula I areseparately listed in table 1, but without being restricted thereby.

TABLE 1 substitute R₁ (R₂, R₃, R₄, R₅, R₆) R₁ (R₂, R₃, R₄, R₁ (R₂, R₃,R₄, R₁ (R₂, R₃, R₄, R₅, R₅, R₆) R₅, R₆) R₆) R₁ (R₂, R₃, R₄, R₅, R₆) HNH(CH₂)₃CH₃ OCONHCH₂CH₃ Ph-2,3-2CN-4,5,6-3Cl F NHC(CH₃)₃ OCON(CH₂CH₃)₂Ph-2,3-2CN-3,5,6-3Cl Cl

OCONH(CH₂)₂CH₃ OPh Br

OCONHCH(CH₃)₂ CONHPh-2-Cl-4-CF₃ I

OCONH(CH₂)₃CH₃ CONHPh-2-Cl-4-NO₂ CN

OCONHC(CH₃)₃ CH₂Ph NO₂ CH₂CH═CH₂ CSNH₂ CH₂—Ph-4-Cl OH CH₂CH═CF₂ CSNHCH₃CH₂CH₂Ph NH₂ CH₂CH₂CH═CF₂ CSN(CH₃)₂ CH₂CH₂—Ph-4-Cl CHO CH₂CH₂CF═CF₂CSNHCH₂CH₃ OCH₂Ph COOH CH₂CH═CCl₂ CSN(CH₂CH₃)₂ OCH₂CH₂Ph CO₂Na CH₂C≡CHCSNH(CH₂)₂CH₃ CH₂OCH₂Ph CO₂NH₄ CH₂C≡C—I CSNHCH(CH₃)₂ CH₂OCH₂CH₂Ph CH₃CH₂C≡C—Cl CSNH(CH₂)₃CH₃ CH₂OPh CH₂CH₃ CH₂C≡CCH₃ CSNHC(CH₃)₃ naphthyloxyn-C₃H₇ OCH₂CH═CH₂ SO₂NH₂ naphthylmethyl i-C₃H₇ OCH₂CH═CCl₂ SO₂NHCH₃6-chloropyridin-3-yl i-C₃H₇CH₂CH₂ OCH₂C≡CH SO₂N(CH₃)₂3-Cl-5-CF₃-pyridin-2-yl n-C₄H₉ SO₂CH₃ C(═NOCH₃)CH₃ 5-CF₃-pyridin-2-yli-C₄H₉ SO₂CH₂CH₃ Ph 3,5,6-Cl₃-pyridin-2-yl n-C₅H₁₁ SOCH₃ Ph-2-F3,5-Cl₂-pyridin-2-yl n-C₆H₁₃ SOCH₃CH₃ Ph-3-F 5-OCF₃-pyridin-2-yl CH₂Bu-tCOCH₃ Ph-4-F 6-Cl-pyridazin-3-yl CF₃ COCH₂CH₃ Ph-2-Cl6-CF₃-pyridazin-3-yl CHF₂ COCF₃ Ph-3-Cl 6-OCF₃-pyridazin-3-yl CH₂FCOCH₂Cl Ph-4-Cl 3-Cl-pyrazin-2-y CH₂Cl COCH₂CH₂Cl Ph-4-CH₃6-Cl-pyrazin-2-y CH₂Br OCOCH₃ Ph-3-CH₃ pyrimidin-2-yl CH₂CF₃ OCOCH₂CH₃Ph-2-OCH₃ pyrimidin-4-yl CF₂CHF₂ NHCOCH₃ Ph-3-OCH₃ pyrimidin-5-yl CF₂CF₃NHCOCH₂CH₃ Ph-4-OCH₃ 5-Cl-pyrimidin-2-yl

OSO₂CH₃ Ph-2-CF₃ 5-CF₃-pyrimidin-2-yl

OSO₂CH₂CH₃ Ph-3-CF₃ 5-OCH₃—CO-pyridin-2-yl

CO₂CH₃ Ph-4-CF₃ 4,6-(CH₃)₂-pyrimidin-2-yl OCH₃ CO₂CH₂CH₃ Ph-2-OCF₃4,6-(OCH₃)₂-pyrimidin-2-yl OCH₂CH₃ CO₂CH₂CH₂Cl Ph-3-OCF₃4,6-(CH₃)₂-triazin-2-yl O(CH₂)₂CH₃ SO₂NH₂ Ph-4-OCF₃4,6-(OCH₃)₂-triazin-2-yl OCH(CH₃)₂ SO₂NHCH₃ Ph-4-NO₂5-Cl-benzoxazol-2-yl OCF₃ SO₂N(CH₃)₂ Ph-4-CN 6-Cl-quinoxalin-2-ylOCH₂CF₃ NHCOOCH₃ Ph-4-t-Bu 4-CH₃-benzyl OCF₂CF₃ NHCOOCH₂CH₃ Ph-2,4-2Cl2-CN-benzyl SCH₃ CH₂CO₂CH₃ Ph-2,4-2F 2-Cl-6-F-benzyl CH₂OCH₃CH₂CO₂CH₂CH₃ Ph-3,5-2Cl 2,5-Cl₂-benzyl CH₂OCH₂CH₃ OCH₂CO₂CH₃ Ph-3,4-2Cl6-Cl-pyridin-3-ylmethyl CH₂OCH₂Cl CH₂NHCH₃ Ph-2,3-2Cl2-Ck-thiazol-5-ylmethyl CH₂OCH₂CHF₂ CH₂N(CH₃)₂ Ph-2,5-2Clbenzoxazol-2-yloxy CH₂OCH₂CF₃ CONH₂ Ph-2,6-2Cl5-Cl-benzoxazol-2-ylmethyl CH₂SCH₃ CONHCH₃ Ph-2-CH₃-4-Cl3-Cl-5-CF₃-pyridin-2-yloxy CH₂SCH₂CH₃ CON(CH₃)₂ Ph-2-Cl-4-CF₃6-Cl-pyridn-3-ylmethoxyl CH₂SCH₂Cl CONHCH₂CH₃ Ph-3,4-(OMe)₂2-Cl-thiazol-5-ylmethoxy CH₂SCH₂CHF₂ CON(CH₂CH₃)₂ Ph-2,6-2Cl-4-CF₃5-CH₂Cl-pyridin-2-yloxymethyl NHCH₃ CONH(CH₂)₂CH₃ Ph-2,6-2Cl-4-NO₂6-Cl-pyridin-3-ylmethoxymethyl N(CH₃)₂ CONHCH(CH₃)₂ Ph-2,4,6-3Cl6-Cl-pyridn-3-yl(C═O) NHCH₂CH₃ CONH(CH₂)₃CH₃ Ph-2,4,6-3CH₃pyridn-2-ylO(C═O) N(CH₂CH₃)₂ CONHC(CH₃)₃ Ph-2-CH₃-3-Cl-4,6-2NO₂pyridn-3-yl NH(C═O) NH(CH₂)₂CH₃ OCONHCH₃ Ph-3-Cl-2,6-2NO₂-4-CF₃NHCH(CH₃)₂ OCON(CH₃)₂ Ph-2,5-2CN-3,4,6-3Cl R₁, R₂ CH₂CH₂CH₂ CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂

The present invention is also explained by the following compoundshaving general formula I with antitumor activity in Table 2-Table 53,but without being restricted thereby.

When Ar is Ar1, Q is Q₁, the presentitive compounds 2-1 to 2-112 arelisted in Table 2.

TABLE 2 substituents when Ar = Ar1

No. R₁ R₃ R₄ R₅ R₆ 2-1 H H H H H 2-2 CH₃ H H H H 2-3 C₂H₅ H H H H 2-4i-C₃H₇ H H H H 2-5 n-C₃H₇ H H H H 2-6 n-C₄H₉ H H H H 2-7 t-C₄H₉ H H H H2-8 OCH₃ H H H H 2-9 OC₂H₅ H H H H 2-10 CH₂Cl H H H H 2-11 CH₂NH₂ H H HH 2-12 CH₂CH₂NH₂ H H H H 2-13 CH₂CH₂CN H H H H 2-14 NH₂ H H H H 2-15 NO₂H H H H 2-16 OH H H H H 2-17 CO₂H H H H H 2-18 F H H H H 2-19 Cl H H H H2-20 Br H H H H 2-21 I H H H H 2-22 CH₂—CH═CH₂ H H H H 2-38 CH₂—C≡CH H HH H 2-39 H CH₃ H H H 2-40 H C₂H₅ H H H 2-41 H i-C₃H₇ H H H 2-42 H n-C₃H₇H H H 2-43 H n-C₄H₉ H H H 2-44 H t-C₄H₉ H H H 2-45 H OCH₃ H H H 2-46 HOC₂H₅ H H H 2-47 H CH₂Cl H H H 2-48 H CO₂H H H H 2-49 H F H H H 2-50 HCl H H H 2-51 H Br H H H 2-52 H I H H H 2-53 H Ph H H H 2-54 H H CH₃ H H2-55 H H C₂H₅ H H 2-56 H H i-C₃H₇ H H 2-57 H H n-C₃H₇ H H 2-58 H Hn-C₄H₉ H H 2-59 H H t-C₄H₉ H H 2-60 H H OCH₃ H H 2-61 H H OC₂H₅ H H 2-62H H NH₂ H H 2-63 H H OH H H 2-64 H H CO₂H H H 2-65 H H F H H 2-66 H H ClH H 2-67 H H Br H H 2-68 H H I H H 2-69 H H Ph H H 2-70 H H H CH₃ H 2-71H H H C₂H₅ H 2-72 H H H i-C₃H₇ H 2-73 H H H n-C₃H₇ H 2-74 H H H n-C₄H₉ H2-75 H7 H H t-C₄H₉ H 2-76 H H H OCH₃ H 2-77 H H H OC₂H₅ H 2-78 H H HCH₂Cl H 2-79 H H H N(CH₃)₂ H 2-80 H H H OCOOCH₃ H 2-81 H H H OCOCH₃ H2-82 H H H NH₂ H 2-83 H H H CN H 2-84 H H H OH H 2-85 H H H CO₂H H 2-86H H H F H 2-87 H H H Cl H 2-88 H H H Br H 2-89 H H H I H 2-90 H H HCH₂—CH═CH₂ H 2-91 H H H CH₂—C≡CH H 2-92 H H H H CH₃ 2-93 H H H H C₂H₅2-94 H H H H OCH₃ 2-95 H H H H CHO 2-96 H H H H F 2-97 H H H H Cl 2-98 HH H H Br 2-99 H H H H I 2-100 H H H H Ph 2-101 H H H H CH₂Ph 2-102 CH₃ HH H CH₃ 2-103 H H CH₃ CH₃ H 2-104 H H CH₃ H CH₃ 2-105 H H OCH₃ H OCH₃2-106 H H Cl H Cl 2-107 H H H CH₃ CH₃ 2-108 CH₃ H H CH₃ H 2-109 H H ClCH₃ H 2-110 H H C₂H₅ C₂H₅ H 2-111 CH₃ H CH₃ H H 2-112 H CH₃ CH₃ H CH₃

Table 3: When Ar is Ar1, Q is Q₂, the substituents of presentitivecompounds 3-1 to 3-112 are consistent with 2-1 to 2-112 in Table 2;

Table 4: When Ar is Ar1, Q is Q₃, the substituents of presentitivecompounds 4-1 to 4-112 are consistent with 2-1 to 2-112 in Table 2;

Table 5: When Ar is Ar1, Q is Q₄, the substituents of presentitivecompounds 5-1 to 5-112 are consistent with 2-1 to 2-112 in Table 2;

Table 6: When Ar is Ar1, Q is Q₅, the substituents of presentitivecompounds 6-1 to 6-112 are consistent with 2-1 to 2-112 in Table 2;

Table 7: When Ar is Ar1, Q is Q₆, the substituents of presentitivecompounds 7-1 to 7-112 are consistent with 2-1 to 2-112 in Table 2;

Table 8: When Ar is Ar1, Q is Q₇, the substituents of presentitivecompounds 8-1 to 8-112 are consistent with 2-1 to 2-112 in Table 2;

Table 9: When Ar is Ar1, Q is Q₈ is the substituents of presentitivecompounds 9-1 to 9-112 are consistent with 2-1 to 2-112 in Table 2;

Table 10: When Ar is Ar1, Q is Q₉, the substituents of presentitivecompounds 10-1 to 10-112 are consistent with 2-1 to 2-112 in Table 2;

Table 11: When Ar is Ar1, Q is Q₁₉, the substituents of presentitivecompounds 11-1 to 11-112 are consistent with 2-1 to 2-112 in Table 2;

Table 12: When Ar is Ar1, Q is Q₂₀, the substituents of presentitivecompounds 12-1 to 12-112 are consistent with 2-1 to 2-112 in Table 2;

Table 13: When Ar is Ar1, Q is Q₂₁, the substituents of presentitivecompounds 13-1 to 13-112 are consistent with 2-1 to 2-112 in Table 2;

Table 14: When Ar is Ar1, Q is Q₂₂, the substituents of presentitivecompounds 14-1 to 14-112 are consistent with 2-1 to 2-112 in Table 2.

When Ar is Ar2, Q is Q₁, the presentitive compounds 15-1 to 15-121 arelisted in Table 15.

TABLE 15 substituents when Ar = Ar2

No. R₁ R₂ R₃ R₅ R₆ 15-1 H H H H H 15-2 CH₃ H H H H 15-3 C₂H₅ H H H H15-4 i-C₃H₇ H H H H 15-5 n-C₃H₇ H H H H 15-6 n-C₄H₉ H H H H 15-7 t-C₄H₉H H H H 15-8 OH H H H H 15-9 NH₂ H H H H 15-10 CN H H H H 15-11 NO₂ H HH H 15-12 CHO H H H H 15-13 CO₂H H H H H 15-14 COCH₃ H H H H 15-15 CONH₂H H H H 15-16 COOCH₃ H H H H 15-17 CH₂COCH₃ H H H H 15-18 CH₂—CH═CH₂ H HH H 15-19 C(CH₃)₂—CH═CH₂ H H H H 15-20 4-Cl—Ph H H H H 15-21 4-CH₃—Ph HH H H 15-22 H CH₃ H H H 15-23 H C₂H₅ H H H 15-24 H i-C₃H₇ H H H 15-25 Hn-C₃H₇ H H H 15-26 H n-C₄H₉ H H H 15-27 H t-C₄H₉ H H H 15-28 H OCH₃ H HH 15-29 H OC₂H₅ H H H 15-30 H CH₂Cl H H H 15-31 H CH₂NH₂ H H H 15-32 HCH₂CH₂NH₂ H H H 15-33 H COOCH₃ H H H 15-34 H COCH₃ H H H 15-35 HCH₂COCH₃ H H H 15-36 H OH H H H 15-37 H 4-t-C₄H₉—Ph H H H 15-38 H4-Cl—Ph H H H 15-39 H 4-CH₃—Ph H H H 15-40 H H CH₃ H H 15-41 H H C₂H₅ HH 15-42 H H i-C₃H₇ H H 15-43 H H n-C₃H₇ H H 15-44 H H n-C₄H₉ H H 15-45 HH t-C₄H₉ H H 15-46 H H OH H H 15-47 H H NH₂ H H 15-48 H H CN H H 15-49 HH NO₂ H H 15-50 H H CHO H H 15-51 H H CO₂H H H 15-52 H H COCH₃ H H 15-53H H CH₂N(CH₃)₂ H H 15-54 H H CH₂—CH═CH₂ H H 15-55 H H C(CH₃)₂—CH═CH₂ H H15-56 H H F H H 15-57 H H Cl H H 15-58 H H Br H H 15-59 H H I H H 15-60H H H CH₃ H 15-61 H H H C₂H₅ H 15-62 H H H i-C₃H₇ H 15-63 H H H n-C₃H₇ H15-64 H H H n-C₄H₉ H 15-65 H H H t-C₄H₉ H 15-66 H H H OCH₃ H 15-67 H H HOC₂H₅ H 15-68 H H H CH₂Cl H 15-69 H H H COCH₃ H 15-70 H H H NH₂ H 15-71H H H NO₂ H 15-72 H H H OH H 15-73 H H H OCOCH₃ H 15-74 H H H F H 15-75H H H Cl H 15-76 H H H Br H 15-77 H H H I H 15-78 H H H CH₂—CH═CH₂ H15-79 H H H CH₂—C≡CH H 15-80 H H H H CH₃ 15-81 H H H H C₂H₅ 15-82 H H HH i-C₃H₇ 15-83 H H H H n-C₃H₇ 15-84 H H H H n-C₄H₉ 15-85 H H H H t-C₄H₉15-86 H H H H OCH₃ 15-87 H H H H OC₂H₅ 15-88 H H H H OH 15-89 H H H HC(NOCH₃)CH₃ 15-90 H H H H F 15-91 H H H H Cl 15-92 H H H H Br 15-93 H HH H I 15-94 H H H H CH₂—CH═C(CH₃)₂ 15-95 H CH₃ H H CH₃ 15-96 H Ph H HCH₃ 15-97 H Ph H H OCH₃ 15-98 H CH₂Cl H H Ph 15-99 H H CH₃ H CH₃ 15-100H H OCH₃ H OCH₃ 15-101 CH₃ H H OCH₃ H 15-102 CH₃ H H CH═CH₂Ph H 15-103 HCH₃ CH₃ H H 15-104 CH₃ CH₃ H H H 15-105 Ph CH₃ H H H 15-106 H CH₃ OCH₃ HH 15-107 H CH₃ Cl H H 15-108 H CH₃ H H t-C₄H₉ 15-109 H H H OCH₃ OCH₃15-110 H H CH₃ CH₃ CH₃ 15-111 H CH₃ H CH₃ CH₃ 15-112 CH₃ CH₃ H CH₃ H15-113 H H OCH₃ OCH₃ OCH₃ 15-114 CH₂CH₂CH₂ H H H 15-115 CH₂CH₂CH₂ H HCH₃ 15-116 CH₂CH₂CH₂ H CH₃ H 15-117 CH₂CH₂CH₂ H Ph H 15-118 CH₂CH₂CH₂CH₂H H H 15-119 CH₂CH₂CH₂CH₂ H H CH₃ 15-120 CH₂CH₂CH₂CH₂ H CH₃ H 15-121CH₂CH₂CH₂CH₂ H Ph H

Table 16: When Ar is Ar2, Q is Q₂, the substituents of presentitivecompounds 16-1 to 16-121 are consistent with 15-1 to 15-121 in Table 15;

Table 17: When Ar is Ar2, Q is Q₃, the substituents of presentitivecompounds 17-1 to 17-121 are consistent with 15-1 to 15-121 in Table 15;

Table 18: When Ar is Ar2, Q is Q₄, the substituents of presentitivecompounds 18-1 to 18-121 are consistent with 15-1 to 15-121 in Table 15;

Table 19: When Ar is Ar2, Q is Q₅, the substituents of presentitivecompounds 19-1 to 19-121 are consistent with 15-1 to 15-121 in Table 15;

Table 20: When Ar is Ar2, Q is Q₆, the substituents of presentitivecompounds 20-1 to 20-121 are consistent with 15-1 to 15-121 in Table 15;

Table 21: When Ar is Ar2, Q is Q₇, the substituents of presentitivecompounds 21-1 to 21-121 are consistent with 15-1 to 15-121 in Table 15;

Table 22: When Ar is Ar2, Q is Q₈, the substituents of presentitivecompounds 22-1 to 22-121 are consistent with 15-1 to 15-121 in Table 15;

Table 23: When Ar is Ar2, Q is Q₉, the substituents of presentitivecompounds 23-1 to 23-121 are consistent with 15-1 to 15-121 in Table 15;

Table 24: When Ar is Ar2, Q is Q₁₉, the substituents of presentitivecompounds 24-1 to 24-121 are consistent with 15-1 to 15-121 in Table 15;

Table 25: When Ar is Ar2, Q is Q₂₀, the substituents of presentitivecompounds 25-1 to 25-121 are consistent with 15-1 to 15-121 in Table 15;

Table 26: When Ar is Ar2, Q is Q₂₁, the substituents of presentitivecompounds 26-1 to 26-121 are consistent with 15-1 to 15-121 in Table 15;

Table 27: When Ar is Ar2, Q is Q₂₂, the substituents of presentitivecompounds 27-1 to 27-121 are consistent with 15-1 to 15-121 in Table 15;

When Ar is Ar3, Q is Q₁, the presentitive compounds 28-1 to 28-139 arelisted in Table 28.

TABLE 28 substituents when Ar = Ar3

NO. R₁ R₂ R₄ R₆ 28-1 H H H H 28-2 H CH₃ H H 28-3 H CH₃ H CH₃ 28-4 H Ph HCH₃ 28-5 CH₃ CH₃ H H 28-6 CH₃ CH₃ H CH₃ 28-7 H CF₃ H H 28-8 H CH₃ H E28-9 H CH₃ E H 28-10 H CH₃ COCH₃ H 28-11 H CH₃ H COCH₃ 28-12 Cl CH₃ H H28-13 H CH₂Cl H H 28-14 Cl CH₂Cl H H 28-15 Cl CH₂OCH₃ H H 28-16 ClCH₂CH₃ H H 28-17 H CH₂CH₃ H CH₃ 28-18 C₂H₅ CH₃ H H 28-19 H CH₂OCH₃ H H28-20 H CH₂OC₂H₅ H H 28-21 Cl CH₂OC₂H₅ H H 28-22 OCH₃ CH₂OCH₃ H H 28-23N(CH₃)₂ CH₃ H H 28-24 CN H H H 28-25 Cl CH₃ H CH₃ 28-26 H CH(CH₃)₂ H H28-27 C₃H₇ CH₃ H H 28-28 H t C₄H₉ H H 28-29 H 4-Cl—Ph H H 28-30 Cl4-Cl—Ph H H 28-31 H 4-Cl—Ph H CH₃ 28-32 Cl Ph H H 28-33 H CH₂CH₃ H H28-34 H CH₂C₂H₅ H H 28-35 H CH₂C₂H₅ H CH₃ 28-36 Cl CH₂C₂H₅ H H 28-37 CH₃CH₂C₂H₅ H H 28-38 H 4-F—Ph H H 28-39 Cl 4-F—Ph H H 28-40 H 4-F—Ph H CH₃28-41 H 4-CF₃—Ph H H 28-42 Cl 4-CF₃—Ph H H 28-43 Cl CH₂N(CH₃)₂ H H 28-44OCH₃ C₂H₅ H H 28-45 OCH₃ CH₃ H H 28-46 OC₂H₅ CH₃ H H 28-47 H CH₂OCH₂CF₃H H 28-48 Cl CH₂OCH₂CF₃ H H 28-49 F CF₃ H H 28-50 F CH₃ H H 28-51 HCH₂N(CH₃)₂ H H 28-52 H Ph H H 28-53 Cl Cl H H 28-54 F Cl H H 28-55 HCH₂OCH₂Ph E H 28-56 OCH₃ 4-Cl—Ph H H 28-57 F 4-Cl—Ph H H 28-58 H M H H28-59 Cl M H H 28-60 Cl M H CH₃ 28-61 CH₂S CH₃ H H 28-62 CH₃SO₂ CH₃ H H28-63 F F H H 28-64 CH₃SO₂ Cl H H 28-65 H 4-NO₂—Ph H H 28-66 Cl 4-NO₂—PhH H 28-67 H 4-NO₂—Ph H CH₃ 28-68 PhCH₂ CH₃ H H 28-69 PhCH₂ CH₃ H CH₃28-70 CF₃CH₂O C₃H₇ H H 28-71 i-C₃H₇ CH₃ H H 28-72 n-C₆H₁₃ CH₃ H H 28-73n-C₅H₁₁ CH₃ H H 28-74 C₂H₄—i-Pr CH₃ H H 28-75 n-C₆H₁₃ CH₃ H H 28-76 Hn-C₄H₉ H H 28-77 H n-C₅H₁₁ H H 28-78 H CH(CH₃)₂ H CH₃ 28-79 n-C₃H₇n-C₃H₇ H H 28-80 CH₃ n-C₄H₉ H H 28-81 C₂H₅ n-C₄H₉ H H 28-82 C₃H₇ n-C₄H₉H H 28-83 i-C₃H₇ n-C₄H₉ H H 28-84 n-C₄H₉ n-C₄H₉ H H 28-85 CH₃ n-C₅H₁₁ HH 28-86 C₂H₅ n-C₅H₁₁ H H 28-87 C₃H₇ n-C₅H₁₁ H H 28-88 i-C₃H₇ n-C₅H₁₁ H H28-89 n-C₄H₉ n-C₅H₁₁ H H 28-90 H n-C₆H₁₃ H H 28-91 CH₃ n-C₆H₁₃ H H 28-92C₂H₅ n-C₆H₁₃ H H 28-93 C₃H₇ n-C₆H₁₃ H H 28-94 i-C₃H₇ n-C₆H₁₃ H H 28-95n-C₄H₉ n-C₆H₁₃ H H 28-96 H CH₂—Ph-4-Cl H H 28-97 CH₃ CH₂—Ph-4-Cl H H28-98 C₂H₅ CH₂—Ph-4-Cl H H 28-99 CH₂—Ph-4-Cl CH₃ H H 28-100 CH₂—Ph-4-ClC₂H₅ H H 28-101 CH₂—Ph-4-Cl C₃H₇ H H 28-102 CH₃ CF₃ H H 28-103 Cl CF₃ HH 28-104 C₂H₅ CF₃ H H 28-105 n-C₃H₇ CF₃ H H 28-106 n-C₄H₉ CF₃ H H 28-107H CH₂CH₂—Ph- H H 28-108 CH₃ 4-Cl H H 28-109 H CH₂Bu-t H H 28-110 CH₃CH₂Bu-t H H 28-111 n-C₃H₇ CH₂Bu-t H H 28-112 CH₂Bu-t CH₃ H H 28-113CH₂CH₂—Ph- CH₃ H H 28-114 4-Cl C₂H₅ H H 28-115 C₃H₇ H H 28-116 CO₂CH₃CH₃ H H 28-117 CO₂CH₃ CF₃ H H 28-118 CO₂C₂H₅ C₂H₅ H H 28-119 CO₂C₂H₅n-C₃H₇ H H 28-120 CONHCH₃ CH₃ H H 28-121 CONHC₂H₅ CH₃ H H 28-122CON(CH₃)₂ CH₃ H H 28-123 CH₃ CO₂CH₃ H H 28-124 H 6-Cl—Py-3-yl H H 28-125CH₂CH₂CH₂ H H 28-126 CH₂CH₂CH₂ H CH₃ 28-127 CH₂CH₂CH₂ CH₃ H 28-128CH₂CH₂CH₂CH₂ H H 28-129 CH₂CH₂CH₂CH₂ H CH₃ 28-130 CH₂CH₂CH₂CH₂ CH₃ H28-131 CH₂CH₂CH₂CH₂ Ph H 28-132 H 2-Cl—Ph H H 28-133 H 3-Cl—Ph H H28-134 H 4-Br—Ph H H 28-135 H 4-CN—Ph H H 28-136 H 4-CH₃—Ph H H 28-137 H4-OCH₃—Ph H H 28-138 H 4-OCF₃—Ph H H 28-139 H 4-OCH₂CF₃—Ph H H Note: Eis C(CH₃)—NOCH₃; M is C₆H₃-3,4-(OCH₃)₂.

Table 29: When Ar is Ar3, Q is Q₂, the substituents of presentitivecompounds 29-1 to 29-131 are consistent with 28-1 to 28-139 in Table 28;

Table 30: When Ar is Ar3, Q is Q₃, the substituents of presentitivecompounds 30-1 to 30-131 are consistent with 28-1 to 28-139 in Table 28;

Table 31: When Ar is Ar3, Q is Q₄, the substituents of presentitivecompounds 31-1 to 31-131 are consistent with 28-1 to 28-139 in Table 28;

Table 32: When Ar is Ar3, Q is Q₅, the substituents of presentitivecompounds 32-1 to 32-131 are consistent with 28-1 to 28-139 in Table 28;

Table 33: When Ar is Ar3, Q is Q₆, the substituents of presentitivecompounds 33-1 to 33-131 are consistent with 28-1 to 28-139 in Table 28;

Table 34: When Ar is Ar3, Q is Q₇, the substituents of presentitivecompounds 34-1 to 34-131 are consistent with 28-1 to 28-139 in Table 28;

Table 35: When Ar is Ar3, Q is Q₈, the substituents of presentitivecompounds 35-1 to 35-131 are consistent with 28-1 to 28-139 in Table 28;

Table 36: When Ar is Ar3, Q is Q₉, the substituents of presentitivecompounds 36-1 to 36-131 are consistent with 28-1 to 28-139 in Table 28;

Table 37: When Ar is Ar3, Q is Q₁₉, the substituents of presentitivecompounds 37-1 to 37-131 are consistent with 28-1 to 28-139 in Table 28;

Table 38: When Ar is Ar3, Q is Q₂₀, the substituents of presentitivecompounds 38-1 to 38-131 are consistent with 28-1 to 28-139 in Table 28;

Table 39: When Ar is Ar3, Q is Q₂₁, the substituents of presentitivecompounds 39-1 to 39-131 are consistent with 28-1 to 28-139 in Table 28;

Table 40: When Ar is Ar3, Q is Q₂₂, the substituents of presentitivecompounds 40-1 to 40-131 are consistent with 28-1 to 28-139 in Table 28.

When Ar is Ar4, Q is Q₁, the presentitive compounds 41-1 to 41-116 arelisted in Table 41.

TABLE 41 substituents when Ar = Ar4

No. R₁ R₂ R₃ R₄ R₅ 41-1 H H H H H 41-2 CH₃ H H H H 41-3 C₂H₅ H H H H41-4 i-C₃H₇ H H H H 41-5 n-C₃H₇ H H H H 41-6 n-C₄H₉ H H H H 41-7 t-C₄H₉H H H H 41-8 OH H H H H 41-9 NH₂ H H H H 41-10 CN H H H H 41-11 NO₂ H HH H 41-12 CHO H H H H 41-13 CO₂H H H H H 41-14 COCH₃ H H H H 41-15 CONH₂H H H H 41-16 COOCH₃ H H H H 41-17 CH₂COCH₃ H H H H 41-18 CH₂—CH═CH₂ H HH H 41-19 C(CH₃)₂—CH═CH₂ H H H H 41-20 4-Cl—Ph H H H H 41-21 4-CH₃—Ph HH H H 41-22 H CH₃ H H H 41-23 H C₂H₅ H H H 41-24 H i-C₃H₇ H H H 41-25 Hn-C₃H₇ H H H 41-26 H n-C₄H₉ H H H 41-27 H t-C₄H₉ H H H 41-28 H OCH₃ H HH 41-29 H OC₂H₅ H H H 41-30 H CH₂Cl H H H 41-31 H CH₂NH₂ H H H 41-32 HCH₂CH₂NH₂ H H H 41-33 H COOCH₃ H H H 41-34 H COCH₃ H H H 41-35 HCH₂COCH₃ H H H 41-36 H OH H H H 41-37 H 4-t-C₄H₉—Ph H H H 41-38 H4-Cl—Ph H H H 41-39 H 4-CH₃—Ph H H H 41-40 H H CH₃ H H 41-41 H H C₂H₅ HH 41-42 H H i-C₃H₇ H H 41-43 H H n-C₃H₇ H H 41-44 H H n-C₄H₉ H H 41-45 HH t-C₄H₉ H H 41-46 H H OH H H 41-47 H H NH₂ H H 41-48 H H CN H H 41-49 HH NO₂ H H 41-50 H H CHO H H 41-51 H H CO₂H H H 41-52 H H COCH₃ H H 41-53H H CH₂N(CH₃)₂ H H 41-54 H H CH₂—CH═CH₂ H H 41-55 H H C(CH₃)₂—CH═CH₂ H H41-56 H H F H H 41-57 H H Cl H H 41-58 H H Br H H 41-59 H H I H H 41-60H H H CH₃ H 41-61 H H H C₂H₅ H 41-62 H H H i-C₃H₇ H 41-63 H H H n-C₃H₇ H41-64 H H H n-C₄H₉ H 41-65 H H H t-C₄H₉ H 41-66 H H H OCH₃ H 41-67 H H HOC₂H₅ H 41-68 H H H CH₂Cl H 41-69 H H H COCH₃ H 41-70 H H H NH₂ H 41-71H H H NO₂ H 41-72 H H H OH H 41-73 H H H OCOCH₃ H 41-74 H H H F H 41-75H H H Cl H 41-76 H H H Br H 41-77 H H H I H 41-78 H H H CH₂—CH═CH₂ H41-79 H H H CH₂—C≡CH H 41-80 H H H H CH₃ 41-81 H H H H C₂H₅ 41-82 H H HH i-C₃H₇ 41-83 H H H H n-C₃H₇ 41-84 H H H H n-C₄H₉ 41-85 H H H H t-C₄H₉41-86 H H H H OCH₃ 41-87 H H H H OC₂H₅ 41-88 H H H H OH 41-89 H H H HC(NOCH₃)CH₃ 41-90 H H H H F 41-91 H H H H Cl 41-92 H H H H Br 41-93 H HH H I 41-94 H H H H CH₂—CH═C(CH₃)₂ 41-95 H CH₃ H H CH₃ 41-96 H Ph H HCH₃ 41-97 H Ph H H OCH₃ 41-98 H CH₂Cl H H Ph 41-99 H H CH₃ H CH₃ 41-100H H OCH₃ H OCH₃ 41-101 CH₃ H H OCH₃ H 41-102 CH₃ H H CH═CH₂Ph H 41-103 HCH₃ CH₃ H H 41-104 CH₃ CH₃ H H H 41-105 Ph CH₃ H H H 41-106 H H OCH₃ HOCH₃ 41-107 H CH₃ Cl H H 41-108 H CH₃ H H CH₃ 41-109 H H H OCH₃ OCH₃41-110 H CH₃ CH₃ H OCH₃ 41-111 CH₂CH₂CH₂ H H H 41-112 CH₂CH₂CH₂ H H CH₃41-113 CH₂CH₂CH₂ H H OCH₃ 41-114 CH₂CH₂CH₂CH₂ H H H 41-115 CH₂CH₂CH₂CH₂H H CH₃ 41-116 CH₂CH₂CH₂CH₂ H H OCH₃

Table 42: When Ar is Ar4, Q is Q₂, the substituents of presentitivecompounds 42-1 to 42-116 are consistent with 41-1 to 41-116 in Table 41;

Table 43: When Ar is Ar4, Q is Q₃, the substituents of presentitivecompounds 43-1 to 43-116 are consistent with 41-1 to 41-116 in Table 41;

Table 44: When Ar is Ar4, Q is Q₄, the substituents of presentitivecompounds 44-1 to 44-116 are consistent with 41-1 to 41-116 in Table 41;

Table 45: When Ar is Ar4, Q is Q₅, the substituents of presentitivecompounds 45-1 to 45-116 are consistent with 41-1 to 41-116 in Table 41;

Table 46: When Ar is Ar4, Q is Q₆, the substituents of presentitivecompounds 46-1 to 46-116 are consistent with 41-1 to 41-116 in Table 41;

Table 47: When Ar is Ar4, Q is Q₇, the substituents of presentitivecompounds 47-1 to 47-116 are consistent with 41-1 to 41-116 in Table 41;

Table 48: When Ar is Ar4, Q is Q₈, the substituents of presentitivecompounds 48-1 to 48-116 are consistent with 41-1 to 41-116 in Table 41;

Table 49: When Ar is Ar3, Q is Q₉, the substituents of presentitivecompounds 49-1 to 49-116 are consistent with 41-1 to 41-116 in Table 41;

Table 50: When Ar is Ar3, Q is Q₁₉, the substituents of presentitivecompounds 50-1 to 50-116 are consistent with 41-1 to 41-116 in Table 41;

Table 51: When Ar is Ar3, Q is Q₂₀, the substituents of presentitivecompounds 51-1 to 51-116 are consistent with 41-1 to 41-116 in Table 41;

Table 52: When Ar is Ar3, Q is Q₂₁, the substituents of presentitivecompounds 52-1 to 52-116 are consistent with 41-1 to 41-116 in Table 41;

Table 53: When Ar is Ar3, Q is Q₂₂, the substituents of presentitivecompounds 53-1 to 53-116 are consistent with 41-1 to 41-116 in Table 41.

Some commercial (or under development) substituent benzyloxy groupcontaining ether compounds used as fungicides in agrochemical field aresummarized as follows (Table 54):

azoxystrobin kresoxim-methyl metominostrobin picoxystrobintrifloxstrobin pyraoxystrobin Dimoxystrobin (fluoxastrobin) orysastrobinenoxastrobin (SSF 129) flufenoxystrobin (pyrametostrobin)(triclopyricarb) fenaminstrobin pyraclostrobin

The most preferred substituent benzyloxy group containing ethercompounds applied as antitumor drugs of general formula I are: compounds28-5 (jiaxiangjunzhi), 28-72 (coumoxystrobin), 28-18, 28-128, 28-129 andpyraoxystrobin.

The compounds having formula I in present invention have been reportedin prior art, which are commercial available or can be preparedaccording to the following literatures U.S. Pat. No. 7,642,364,CNP1869032, Pest Manag. Sci. 2011, 67, 647, Nat. Prod. Commun. 2011, 6,1917, Chin. Chem. Lett. 2011, 22, 663, Chin. J. Pestic. 2011, 50, 90.

The present invention includes the formulations, which were made fromthe compounds having the general formula I as active ingredient, andpreparation thereof. The preparation of formulations: Dissolve thecompounds of present invention in water soluble organic solvents, thenon-ionicity of surfactant, water soluble lipid, all kinds ofcyclodextrin, fatty acid, fatty acid ester, phospholipids or theircombination solvents, then 1-20% of carbohydrates were obtained byadding physiological saline. Mentioned organic solvents includepolyethylene glycol (PEG), ethanol, propylene glycol or theircombination solvents.

The compounds having the general formula I in present invention andtheir isomers and prodrug can be used to prepare the drugs orformulations to cure, prevent or alleviate cancer. The activeingredients are composed of one or more than two substituent benzyloxygroup containing ether compounds having the general formula I.Especially to cure or alleviate the cancer causing by cancer cells ofhuman tissue or organ. The preferred cancers are: colon cancer, livercancer, lymph cancer, lung cancer, esophageal cancer, breast cancer,central nervous system cancer, melanoma, ovarian cancer, cervicalcancer, renal cancer, leukemia, prostatic cancer, pancreatic cancer,bladder cancer, rectal cancer, or stomach cancer, etc.

The compounds in present invention can be used as active ingredients ofantitumor drug, which can be used alone or combined with otherantitumor/antiviral drugs. The drug combination process in presentinvention, using at least one of the compounds and its activederivatives with other one or more antitumor/antiviral drugs, are usedtogether to increase the overall effect. The dose and drugadministration time of combination therapy are based on the mostreasonable treatment effect in the different situations.

The formulations include the effective dose of the compounds havinggeneral formula I. The “effective dose” refers to the compound dosage,which are effective to cure cancer. The effective dose or dose can bedifferent based on the suggestions of experienced person at differentconditions. For instance, the different usage of drug based on differentcancers; the dose of drug also can be changed based on whether it shareswith other therapeutic method, such as antitumor or antiviral drugs. Thedrug can be prepared for any useable formulations. The salts ofcompounds also can be used if the alkaline or acidic compounds canformed the non-toxic acids or salts. The organic acids/salts in pharmacyinclude anion salts, which are formed with acids, such asp-toluenesulfonic acid, methylsulfonic acid, acetic acid, benzoic acid,citric acid, malic acid, tartaric acid, maleic acid, succinic acid,ascorbic acid or glycerophosphoric acid; the inorganic salts includechloride, bromide, fluoride, iodide, sulfate, nitrate, bicarbonate,carbonate or phosphate. For example, the alkaline compounds, such asamines can form salts with suitable acids; acids can form salts withalkalis or alkaline earth.

The compounds in present invention having general formula I generaleasily dissolve in organic solvent, water soluble solvent and theirmixture with water. The water soluble solvents prefer alcohol,polyethylene glycol, N-methyl-2-pyrrolidone, N, N-dimethyl acetamide, N,N-dimethyl formamide, dimethylsulfoxide, acetonitrile and their mixture.Mentioned alcohols prefer methanol, ethanol, isopropanol, glycerol orethylene glycol. The compounds in present invention mix with common drugcarrier to form formulations. Dissolve the compounds of presentinvention in water soluble organic solvents, aprotic solvent, watersoluble lipid, cyclodextrin, fatty acid, phospholipids or theircombination solvents, then 1-20% of carbohydrates were obtained byadding physiological saline, such as glucose aqueous solution. Thestability formulations made by this way are used for animal andclinical.

The drugs were made from the active ingredients of general formula Icompounds, which can dose by oral medication or parenteral route, alsoby implantable medication pump and other methods. Where the parenteralroute refer to injection or drip technology through subcutaneousintradermal, intramuscular, intravenous, arteries, atrium, synovium,sternum, intrathecal, wound area, encephalic, etc. The formulations weremixed using conventional method by technicist, which are used for animaland clinical, including tablets, pills, capsule, granule, syrup,injection, freeze-dried powder injection, emulsion, powder, freeze-driedpowder, drop pill, milk suspension, aqueous suspension, colloid,colloidal solution, sustained-release suspensions, nanoparticle or otherformulations.

The compounds having the general formula I in present invention can beused to cure or alleviate the cancer causing by cancer cells of humantissue or organ. The cancers include but not limited to colon cancer,liver cancer, lymph cancer, lung cancer, esophageal cancer, breastcancer, central nervous system cancer, melanoma, ovarian cancer,cervical cancer, renal cancer, leukemia, prostatic cancer, pancreaticcancer, bladder cancer, rectal cancer or stomach cancer.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is illustrated by the following examples, butwithout being restricted thereby. (All raw materials are commerciallyavailable unless otherwise specified.)

Antitumor Activity Bioassay

In vitro Cell inhibition assay is as follows:

The human cancer cell lines used for this assay were bladder cancer J82,T24, prostate cancer LNCap, PC-3, lung cancer A549, H157, H460, H520,colon cancer HCT8, HCT116, RkO, and leukemia HL-60, etc.

Example 1

In vitro cell culture technology was selected for the determination ofinhibition rate bladder cancer cell lines J82 and T24, prostate cancercell lines LNCap and PC-3, lung cancer cell lines A549, H157, H460 andH520. 1000 to 3000 cells were inoculated to 24-well plate, followed byaddition of 1 mL culture medium well known to researchers in this fieldto each well, the cells were cultured in 5% incubator for 24 hours at37° C., then the different concentration compounds and controls wereadded to each well. It should be noted that the added volume is not morethan 0.5% of total volume. After completion of addition, the cellscontinued being cultured in incubator for one week, the culture mediumwas removed and washed by cold PBS of 1 mL once, and then fixed for 10minutes at room temperature with 1% formalin, followed by wash with PBSof 1 mL. After fixation, stain was carried out with 0.1% crystal violetfor 30 minutes. 0.1% crystal violet was recycled. The stained cells werewashed gently with deionized water, dried at room temperature andkepted. The inhibition rate was calculated according to the foilingequation. The controls are Selumetinib (AZD6244), Gefitinib, Cisplatin.Inhibition rate=number of left cells each treatment/number of left cellsof untreated control×100%

At the concentration of 10 μM, the inhibition rate of compounds of thisinvention against all tested cell lines attached 90%-100%, some of themwere further tested at lower concentration and the comparative bioassaywas conducted with the controls selumetinib (AZD6244), gefitinib,Cisplatin at the same time, part of test results are listed in Table 55:

TABLE 55 Inhibition rate on human cancer cells Concentration(μM)/Inhibition (%) Cell line Compound No 5.0 2.5 1.0 0.5 0.25 J82 28-5100 100 80 / / 28-72 100 100 95 90 70 Pyraoxystrobin 100 100 100 100 70selumetinib 70 / / / / Cisplatin 20 5 0 0 0 Compound A 100 100 95 50 0Compound B 100 95 90 50 0 Flufenoxystrobin Azoxystrobin 0 / / / / T2428-5 100 100 100 100 100 28-72 100 100 100 100 100 Pyraoxystrobin 100100 100 100 100 Selumetinib 70 / / / / Cisplatin 20 5 0 0 0 Compound A100 100 100 0 / Compourtd B 100 100 100 5 0 FlufenoxystrobinAzoxystrobin 0 / / / / LNCap 28-5 100 100 100 / / 28-72 100 100 100 100100 Pyraoxystrobin 100 100 100 100 100 selumetinib 20 / / / / Compound A100 100 100 0 / Compourtd B 100 50 0 / / Flufenoxystrobin Azoxystrobin 0/ / / / PC-3 28-5 100 100 100 / / 28-72 100 100 100 100 100Pyraoxystrobin 100 100 100 100 100 Selumetinib 0 / / / / Compound A 100100 85 0 / Compourtd B 100 100 50 / / Flufenoxystrobin Azoxystrobin 0 // / / A549 28-5 100 100 80 / / 28-7 90 70 / / / 28-12 100 95 80 / /28-18 100 100 100 90 / 28-27 95 90 80 / / 28-29 95 / / / / 28-33 99 9580 / / 28-34 100 95 90 / / 28-50 90 / / / / 28-52 100 100 95 90 / 28-72100 100 95 90 / 28-75 90 / / / / 28-126 90 85 / / / 28-128 100 100 100100 70 28-129 100 100 100 95 90 28-132 90 / / / / 28-133 100 100 / / /28-134 100 100 28-135 80 / / / / 28-136 100 100 / / / 28-137 100 100 / // 28-137 100 100 / / / Selumetinib 10 0 0 0 0 Gefitinib 20 10 0 0 0Cisplatin 80 30 5 0 0 H157 28-5 100 100 100 100 / 28-72 100 100 100100 >90 AZD6244 20 / / / / H460 28-2 95 / / / / 28-5 100 100 100 100 /28-7 95 80 / / / 28-12 95 90 75 / / 28-18 95 95 95 90 80 28-27 95 95 80/ / 28-29 95 90 70 / / 28-33 95 95 90 / / 28-34 95 95 93 / / 28-41 85 75/ / / 28-50 95 90 70 / / 28-52 100 100 100 90 60 28-72 100 100 100 10095 28-75 95 90 70 / / 28-124 75 / / / / 28-126 95 90 / / / 28-128 100100 100 100 80 28-129 100 100 95 70 / 32-5 95 / / / / 32-6 85 / / / /Selumetinib 60 0 0 0 0 Gefitinib 95 0 0 0 0 Cisplatin 90 30 5 0 0 H52028-5 100 100 90 80 70 28-7 100 80 / / / 28-12 100 100 50 / / 28-18 100100 100 95 50 28-27 100 100 100 95 / 28-29 100 70 70 40 30 28-33 100 90/ / / 28-34 100 100 99 70 / 28-41 70 / / / / 28-50 100 80 60 50 30 28-52100 100 100 100 70 28-72 100 100 100 100 >90 28-75 100 80 / / / 28-12470 / / / / 28-126 95 90 70 / / 28-128 100 100 100 100 70 28-129 100 100100 95 85 Selumetinib 20 / / / / Gefitinib 5 0 0 0 0 Cisplatin 50 30 205 0 HCT 8 28-72 100 100 100 95 / 28-128 100 100 100 100 95 28-129 100100 100 95 80 Selumetinib 50 40 20 / / Gefitinib / 10 5 0 / Cisplatin 9070 50 10 5 HCT 116 28-72 100 100 99 95 80 28-128 100 100 100 100 9528-129 100 100 100 95 90 Selumetinib 90 85 80 75 50 Gefitinib 30 5 0 0 0Cisplatin 50 20 5 0 0 RkO 28-72 100 100 100 100 95 28-128 100 100 100100 99 28-129 100 100 100 99 85 Selumetinib 95 90 85 80 30 Gefitinib /80 75 70 50 Cisplatin 70 50 10 5 0 Note: 1.“/” stands for no data.2.bladder cancer cell lines J82 

  T24, prostate cancer cell lines LNCap 

  PC-3, lung cancer cell lines A549, H157 

  H460 

  H520, clon cancer cell lines HCT8, HCT116, RkO, the culture medium forall cell lines is RMPI-1640.

Example 2

The inhibition rate of human leukemia HL-60 cells was evaluated byregular MTT method. The human leukemia HL-60 cells were picked up fromcell incubator, after washed for twice using PBS, cells were digested by0.25% trypsin, and then add medium to terminate the digestion. Aftercells were collected using centrifuge and re-suspended, counting cellsunder inverted microscope and adding medium to make a density which was5×10⁴ cells/mL. After 100 μL aliquots were added to each well of 96-wellmicrotiter plates, cells were cultured in 5% incubator for overnight at37° C., then the different concentration compounds were added to eachwell. After incubation for 48 h, MTT solution was added to each well andplates were then incubated for 4 h. The MTT tetrazolium was reduced toformazan by living cells. Then the formazan crystals were dissolvedthough adding DMSO to each well. The absorbance was read at 570 nm witha microplate reader.

Part of the test results are listed in Table 56:

TABLE 56 Proliferation inhibitory effect on human leukemia HL-60 cell(%) Concentration (μM) Compound No. 100 10 1  2-1 48.8 0 0 28-2 71.349.2 6.0 28-3 58.8 33.4 4.1 28-5 73.8 59.3 31.7  28-6 52.0 53.0 48.228-7 83.9 71.0 42.3 28-24 86.7 44.5 10.8 28-27 83.9 79.9 59.0 28-38 63.772.9 77.5 28-50 84.8 83.1 47.1 28-68 84.4 62.0 54.6 28-71 50.3 48.2 40.928-72 54.4 47.9 45.3 28-79 71.2 53.1 28.8 28-124 27.8 29.3 0.5 28-12585.0 73.8 47.0 15-22 86.8 51.8 50.3 Note: the culture medium for humanleukemia HL-60 is OPTI-MEM.

The invention claimed is:
 1. A method of treating a subject having acancer selected from the group consisting of colon cancer, lung cancer,leukemia, prostatic cancer, and bladder cancer, which comprisesadministering to the subject a substituent benzyloxy group containingether compound as an antitumor agent, said substituent benzyloxy groupcontaining either compound having general formula I:

wherein: Ar is selected from one of the following groups, Ar2 to Ar3:

Q is selected from one of the following groups, Q1 to Q22:

R₁, R₂, R₃, R₄, R₅, and R₆, are each independently H, halo, CN, NO₂, OH,NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₁₂alkyl, C₁-C₁₂haloalkyl,C₃-C₈cycloalkyl, C₁-C₁₂alkoxy, C₁-C₁₂haloalkoxy, C₁-C₁₂alkylthio,C₁-C₁₂haloalkylthio, C₁-C₁₂alkoxyC₁-C₁₂alkyl,haloC₁-C₁₂alkoxyC₁-C₁₂alkyl, C₁-C₁₂alkoxyC₁-C₁₂alkoxy,haloC₁-C₁₂alkoxyC₁-C₁₂alkoxy, C₁-C₁₂alkylthioC₁-C₁₂alkyl,haloC₁-C₁₂alkylthioC₁-C₁₂alkyl, C₁-C₁₂alkylamino, C₁-C₁₂haloalkylamino,C₂-C₁₂dialkylamino, C₂-C₁₂halodialkylamino, piperidinyl, pyrrolidinyl,N-methylpiperidinyl, morpholinyl, C₂-C₁₂alkenyl, C₂-C₁₂haloalkenyl,C₂-C₁₂alkynyl, C₂-C₁₂haloalkynyl, C₂-C₁₂alkenyloxy,C₂-C₁₂haloalkenyloxy, C₂-C₁₂alkynyloxy, C₂-C₁₂haloalkynyloxy,C₁-C₁₂alkylsulfonyl, C₁-C₁₂haloalkylsulfonyl, C₁-C₁₂alkylsulfinyl,C₁-C₁₂haloalkylsulfinyl, C₁-C₁₂alkylcarbonyl, C₁-C₁₂haloalkylcarbonyl,C₁-C₁₂alkylcarbonyloxy, C₁-C₁₂alkylcarbonylamino,C₁-C₁₂alkylsulfonyloxy, C₁-C₁₂alkoxycarbonyl, C₁-C₁₂haloalkoxycarbonyl,C₁-C₁₂alkylamlinosulfonyl, C₁-C₁₂alkoxycarbonylamino,C₁-C₁₂alkoxycarbonylC₁-C₁₂alkyl, C₁-C₁₂alkoxycarbonylC₁-C₁₂alkoxy,aminoC₁-C₁₂alkyl, C₁-C₁₂alkylaminoC₁-C₁₂alkyl,C₂-C₁₂dialkylaminoC₁-C₁₂alkyl, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁,C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, or R₇; or R1 and R2 are linkedwith a carbon atom to form a six-membered ring; R₇ is unsubstituted orsubstituted phenyl, phenyloxy, phenyloxy C₁-C₁₂alkyl, phenylcarbonyl,phenyloxycarbonyl, phenylaminocarbonyl, phenylC₁-C₁₂alkyl,phenylC₁-C₁₂alkoxy, phenylC₁-C₁₂alkoxyC₁-C₁₂alkyl, naphthyl,naphthyloxy, naphthyloxy C₁-C₁₂alkyl, naphthylcarbonyl, naphthylC₁-C₁₂alkyl, naphthyl C₁-C₁₂alkoxy, naphthyl C₁-C₁₂alkoxyC₁-C₁₂alkyl,heteroaryl, heteroaryloxy, heteroarylC₁-C₁₂alkoxyC₁-C₁₂alkyl,heteroaryloxyC₁-C₁₂alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl,heteroarylaminocarbonyl, heteroarylC₁-C₁₂alkyl orheteroarylC₁-C₁₂alkoxy, which may be optionally substituted by 1 to 5substituents selected from the group consisting of: halo, NO₂, CN, SH,C₁-C₆alkyl, C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₂-C₆alkenyl,C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆alkenyloxy,C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy, C₃-C₆haloalkynyloxy,C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl,C₁-C₆haloalkylsulfonyl, C₁-C₆alkoxyC₁-C₆alkyl, C₁-C₆alkylcarbonyl,C₁-C₆haloalkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆alkylcarbonylamino,C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆alkoxyC₁-C₆alkoxy,C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylamino,C₁-C₆alkoxycarbonylC₁-C₆alkoxy, CHO, CO₂H, CO₂Na, CO₂NH₄, NR₁₀R₁₁,C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, and SO₂NR₁₀R₁₁; R₈ and R₉ areeach independently H, C₁-C₆alkyl, aryl, or aryl C₁-C₆alkyl; R₁₀ and R₁₁are each independently H, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy,C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, or C₃-C₈cycloalkyl;and stereoisomers thereof.
 2. The method according to claim 1, whereinAr is Ar2 or Ar3; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉, Q₁₁, Q₂₀,Q₂₁, or Q₂₂; R₁, R₂, R₃, R₄, R₅, and R₆ are each independently H, halo,CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₆alkyl, C₁-C₆haloalkyl,C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio,C₁-C₆haloalkylthio, C₁-C₆alkoxyC₁-C₆alkyl, haloC₁-C₆alkoxyC₁-C₆alkyl,C₁-C₆alkoxyC₁-C₆alkoxy, haloC₁-C₆alkoxyC₁-C₆alkoxy,C₁-C₆alkylthioC₁-C₆alkyl, haloC₁-C₆alkylthioC₁-C₆alkyl, C₁-C₆alkylamino,C₁-C₆haloalkylamino, C₂-C₈dialkylamino, C₂-C₈halodialkylamino,piperidinyl, pyrrolidinyl, N-methylpiperidinyl, morpholinyl,C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl,C₂-C₆alkenyloxy, C₂-C₆haloalkenyloxy, C₂-C₆alkynyloxy,C₂-C₆haloalkynyloxy, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl,C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylcarbonyl,C₁-C₆haloalkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆alkylcarbonylamino,C₁-C₆alkylsulfonyloxy, C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl,C₁-C₆alkylaminosulfonyl, C₁-C₆alkoxycarbonylamino,C₁-C₆alkoxycarbonylC₁-C₆alkyl, C₁-C₆alkoxycarbonylC₁-C₆alkoxy,aminoC₁-C₆alkyl, C₁-C₆alkylaminoC₁-C₆alkyl, C₂-C₈dialkylaminoC₁-C₆alkyl,C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, orR₇; or R1 and R2 are linked with a carbon atom to form a six-memberedring; R₇ is unsubstituted or substituted phenyl, phenyloxy, phenyloxyC₁-C₆alkyl, phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl,phenylC₁-C₆alkyl, phenylC₁-C₆alkoxy, phenylC₁-C₆alkoxyC₁-C₆alkyl,naphthyl, naphthyloxy, naphthyloxy C₁-C₆alkyl, naphthylcarbonyl,naphthyl C₁-C₆alkyl, naphthyl C₁-C₆alkoxy,naphthylC₁-C₆alkoxyC₁-C₆alkyl, heteroaryl, heteroaryloxy,heteroalyC₁-C₆alkoxyC₁-C₆alkyl, heteroaryloxyC₁-C₆alkyl,heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl,heteroaylC₁-C₆alkyl or heteroarylC₁-C₆alkoxy, which i may be optionallysubstituted by 1 to 5 substituents selected from the group consistingof: halo, NO₂, CN, SH, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₃-C₆cycloalkyl,C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio,C₂-C₄alkenyl, C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl,C₃-C₄alkenyloxy, C₃-C₄haloalkenyloxy, C₃-C₄alkynyloxy,C₃-C₄haloalkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl,C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₁-C₄alkylcarbonyloxy,C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl,C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H,CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, andSO₂NR₁₀R₁₁; R₈ and R₉ are each independently H, C₁-C₄alkyl, aryl, oraryl C₁-C₄alkyl; R₁₀ and R₁₁ are each independently H, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylthio,C₁-C₄haloalkylthio, or C₃-C₆cycloalkyl.
 3. The method according to claim2, wherein Ar is Ar2 or Ar3; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, Q₈, Q₉,Q₁₉, Q₂₀, Q₂₁, or Q₂₂; R₁, R₂, R₃, R₄, R₅, and R₆ are each independentlyH, halo, CN, NO₂, OH, NH₂, CHO, CO₂H, CO₂Na, CO₂NH₄, C₁-C₆alkyl,C₁-C₆haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, C₁-C₄haloalkylthio, C₁-C₄alkoxyC₁-C₄alkyl,haloC₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkoxyC₁-C₄alkoxy,haloC₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkylthioC₁-C₄alkyl,haloC₁-C₄alkylthioC₁-C₄alkyl, C₁-C₄alkylamino, C₁-C₄haloalkylamino,C₂-C₆dialkylamino, C₂-C₆halodialkylamino, piperidinyl, pyrrolidinyl,N-methylpiperidinyl, morpholinyl, C₂-C₄alkenyl, C₂-C₄haloalkenyl,C₂-C₄alkynyl, C₂-C₄haloalkynyl, C₂-C₄alkenyloxy, C₂-C₄haloalkenyloxy,C₂-C₄alkynyloxy, C₂-C₄haloalkynyloxy, C₁-C₄alkylsulfonyl,C₁-C₄haloalkylsulfonyl, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl,C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₁-C₄alkylcarbonyloxy,C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl,C₁-C₄haloalkoxycarbonyl, C₁-C₄alkylaminosulfonyl,C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkoxycarbonylC₁-C₄alkoxy, aminoC₁-C₄alkyl,C₁-C₄alkylaminoC₁-C₄alkyl, C₂-C₆dialkylaminoC₁-C₄alkyl, C(═O)NR₁₀R₁₁,OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, SO₂NR₁₀R₁₁, C(═NOR₉)R₈, or R₇; or R1 and R2are linked with a carbon atom to form a saturated six-membered ring; R₇is unsubstituted or substituted phenyl, phenyloxy, phenyloxy C₁-C₄alkyl,phenylcarbonyl, phenyloxycarbonyl, phenylaminocarbonyl,phenylC₁-C₄alkyl, phenylC₁-C₄alkoxy, phenylC₁-C₄alkoxyC₁-C₄alkyl,naphthyl, naphthyloxy, naphthyloxy C₁-C₄alkyl, naphthylcarbonyl,naphthyl C₁-C₄alkyl, naphthyl C₁-C₄alkoxy,naphthylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryl, heteroaryloxy,heteroarylC₁-C₄alkoxyC₁-C₄alkyl, heteroaryloxyC₁-C₄alkyl,heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylaminocarbonyl,heteroarylC₁-C₄alkyl, or heteroarylC₁-C₄alkoxy, which may be optionallysubstituted by 1 to 5 substituents selected from the group consistingof: halo, NO₂, CN, SH, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₃-C₆cycloalkyl,C₁-C₄alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio,C₂-C₄alkenyl, C₂-C₄haloalkenyl, C₂-C₄alkynyl, C₂-C₄haloalkynyl,C₃-C₄alkenyloxy, C₃-C₄haloalkenyloxy, C₃-C₄alkynyloxy, C₃-C₄haloalkynyloxy, C₁-C₄alkylsulfinyl, C₁-C₄haloalkylsulfinyl,C₁-C₄alkylsulfonyl, C₁-C₄haloalkylsulfonyl, C₁-C₄alkoxyC₁-C₄alkyl,C₁-C₄alkylcarbonyl, C₁-C₄haloalkylcarbonyl, C₁-C₄alkylcarbonyloxy,C₁-C₄alkylcarbonylamino, C₁-C₄alkylsulfonyloxy, C₁-C₄alkoxycarbonyl,C₁-C₄alkoxyC₁-C₄alkoxy, C₁-C₄alkoxycarbonylC₁-C₄alkyl,C₁-C₄alkoxycarbonylamino, C₁-C₄alkoxycarbonylC₁-C₄alkoxy, CHO, CO₂H,CO₂Na, CO₂NH₄, NR₁₀R₁₁, C(═O)NR₁₀R₁₁, OC(═O)NR₁₀R₁₁, C(═S)NR₁₀R₁₁, andSO₂NR₁₀R₁₁; R₈ and R₉ is are each independently H, C₁-C₄alkyl, aryl, oraryl C₁-C₄alkyl; R₁₀ and R₁₁ are each independently H, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄ haloalkoxy, C₁-C₄alkylthio, C₁-C₄haloalkylthio, or C₃-C₆cycloalkyl.
 4. The method according to claim 3,wherein Ar is Ar2 or Ar3; Q is Q₁, Q₂, Q₃, Q₄, Q₅, Q₆, Q₇, or Q₈; R₁,R₂, R₃, R₄, R₅, and R₆ are each independently H, halo, CN, C₁-C₆alkyl,C₁-C₄haloalkyl, C₃-C₆cycloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy,C₁-C₄alkylthio, A C₁-C₄alkoxyC₁-C₄alkyl, C₁-C₄alkylamino,C₂-C₆dialkylamino, C₁-C₄alkylsulfonyl, or R₇; or R1 and R2 are linkedwith a carbon atom to form a saturated six-membered ring; R₇ isunsubstituted or substituted phenyl, benzyl, phenylethyl or heteroaryl,which may be optionally substituted by 1 to 5 substituents selected fromthe group consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 5. The method according to claim 4,wherein Ar is Ar2 or Ar3; Q is Q₁; R₁, R₂, R₃, R₄, R₅, and R₆ are eachindependently H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl, or R₇; or R1 andR2 are linked with a carbon atom to form a saturated six-membered ring;R₇ is unsubstituted or substituted phenyl, benzyl, or heteroaryl, whichmay be optionally substituted by 1 to 5 substituents selected from thegroup consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 6. The method according to claim 5,wherein Ar is Ar3; Q is Q₁; R₁, R₂, R₃, R₄, R₅, and R₆ are eachindependently H, halo, CN, C₁-C₆alkyl, C₁-C₄haloalkyl, or R₇; or R1 andR2 are linked with a carbon atom to form a saturated six-membered ring;R₇ is unsubstituted or substituted phenyl, benzyl, or heteroaryl, whichmay be optionally substituted by 1 to 5 substituents selected from thegroup consisting of: halo, NO₂, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl,C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 7. The method according to claim 6,wherein Ar is Ar3; Q is Q₁; R₁ is H, halo, or C₁-C₆alkyl; R₂ isC₁-C₄alkyl, C₁-C₄haloalkyl, or R₇; or R1 and R2 are linked with a carbonatom to form a saturated six-membered ring; R₃ and R₄ are H; R₆ is H orC₁-C₄alkyl; R₇ is unsubstituted or substituted phenyl, which may beoptionally substituted by 1 to 3 substituents selected from the groupconsisting of: halo, CN, C₁-C₄alkyl, C₁-C₄ haloalkyl, C₁-C₄alkoxy, andC₁-C₄ haloalkoxy.
 8. The method according to claim 7, wherein Ar is Ar3;Q is Q₁; R₁ is H, halo, or C₁-C₆alkyl; R₂ is C₁-C₄alkyl or R₇; or R1 andR2 are linked with a carbon atom to form a saturated six-membered ring;R₃ and R₄ are H; R₆ is H or C₁-C₄alkyl; R₇ is unsubstituted orsubstituted phenyl, which may be optionally substituted by 1 to 2substituents selected from the group consisting of: halo, C₁-C₄alkyl,C₁-C₄alkoxy, and C₁-C₄ haloalkoxy.
 9. The method according to claim 8,wherein Ar is Ar3; Q is Q₁; R₁ is H, F, or C₁-C₄alkyl; R₂ is C₁-C₄alkylor phenyl; or R₁ and R₂ are linked with a carbon atom to form asaturated six-membered ring; R₃ and R₄ are H; R₆ is H or CH₃.
 10. Themethod according to claim 9, wherein Ar is Ar3; Q is Q₁; R₁ is H orC₁-C₄alkyl; R₂ is CH₃ or phenyl; or R₁ and R₂ are linked with a carbonatom to form a saturated six-membered ring; R₃, R₄, R₆ are H.
 11. Themethod according to claim 1, wherein the substituent benzyloxy groupcontaining ether compound is administered, as an active ingredient,orally or parentally, or by implantable medication pump administration.12. The method according to claim 11, wherein the substituent benzyloxygroup containing ether compound is administered as an active ingredientin the form of a tablet, a pill, a capsule, a granule, a syrup, aninjection, or a freeze-dried powder injection.
 13. The method accordingto claim 12, two or more of the substituted benzyloxy group containingether compounds are provided as me active ingredient.